DOXYLAMINE SUCCINATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE (DOXYLAMINE SUCCINATE).
Antagonist at histamine H1 receptors, producing sedative and antihistaminic effects; also possesses anticholinergic properties.
| Metabolism | Primarily hepatic via CYP450 enzymes (CYP2D6, CYP1A2, and others); undergoes N-demethylation and other oxidative pathways. |
| Excretion | Renal excretion of metabolites (30-60% as conjugated metabolites, <5% unchanged). Fecal elimination is minor (<10%). |
| Half-life | Terminal elimination half-life ranges from 10 to 12 hours in adults. In elderly patients, half-life may be prolonged (up to 15-18 hours) due to reduced renal clearance. |
| Protein binding | Approximately 80-90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is 2.5-4.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70-80% due to first-pass metabolism. |
| Onset of Action | Oral administration: Onset of sedation occurs within 30 minutes; peak effect at 1-2.5 hours. |
| Duration of Action | Duration of sedative effect is 6-8 hours. Antihistaminic effects may persist longer (up to 12 hours). Clinical note: Tolerance to sedative effects may develop with continued use. |
| Molecular Weight | 388.46 |
| Action Class | First-generation antihistamine (ethanolamine class); sedating antihistamine. |
6.25 to 25 mg orally every 4 to 6 hours as needed, not to exceed 150 mg per day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No specific dose adjustment recommended; use with caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Children 6-11 years: 3.125 to 6.25 mg orally every 4-6 hours, not to exceed 37.5 mg/day. Children 12 years and older: same as adult dosing. |
| Geriatric use | Initiate at the lowest effective dose (e.g., 6.25 mg) due to increased sensitivity and risk of anticholinergic effects, sedation, and falls. Maximum recommended dose: 100 mg per day. |
| 1st trimester | No well-controlled studies in pregnant women; animal studies not available. Use only if clearly needed and potential benefit justifies potential risk to fetus. Avoid in first trimester as antihistamines have been associated with increased risk of cleft palate. |
| 2nd trimester | Limited data; generally considered safe when used occasionally at recommended doses. No known teratogenic risk in second trimester. |
| 3rd trimester | Use near term may cause respiratory depression or withdrawal symptoms in neonate (e.g., irritability, tremors). Avoid during third trimester unless essential. |
Clinical note
Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE (DOXYLAMINE SUCCINATE).
| Placental transfer | Doxylamine crosses the placenta; degree of transfer not well documented but expected due to low molecular weight and lipophilicity. |
| Breastfeeding | Small amounts excreted in breast milk; considered compatible with breastfeeding by the American Academy of Pediatrics. Monitor infant for drowsiness, irritability, or poor feeding. Avoid high doses or prolonged use. |
■ FDA Black Box Warning
Not applicable; no FDA black box warning.
| Common Effects | Drowsiness, Dizziness, Dry mouth, nose, and throat, Blurred vision, Constipation, Urinary hesitancy, Thickened bronchial secretions, Nausea, Headache |
| Serious Effects | Respiratory depression (especially in children or with overdose), Severe anticholinergic effects (e.g., urinary retention, blurred vision, confusion, delirium), QT prolongation and torsades de pointes (rare, with overdose or predisposing factors), Seizures (with overdose), Rhabdomyolysis (with overdose), Acute angle-closure glaucoma (in susceptible individuals), Paradoxical CNS stimulation (especially in children or elderly) |
Hypersensitivity to doxylamine or any componentConcurrent use of monoamine oxidase inhibitors (MAOIs)
| Precautions | May cause marked drowsiness and impair mental/physical abilities, Avoid alcohol and other CNS depressants, Use with caution in elderly (increased risk of falls, confusion, anticholinergic effects), May exacerbate urinary retention, glaucoma, or hyperthyroidism, Not recommended for use in children under 6 years for insomnia, May cause paradoxical excitation in children or elderly |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Doxylamine succinate is a pregnancy category A antihistamine used for nausea and vomiting of pregnancy (NVP). Studies in pregnant women have not shown an increased risk of congenital malformations. Second and third trimesters: No evidence of fetal harm; safety established for use in NVP. No known teratogenic effects. |
| Fetal Monitoring | No specific maternal or fetal monitoring required for standard use. In overdose or prolonged use, monitor for maternal CNS depression (drowsiness, dizziness) and fetal heart rate if late pregnancy. |
| Fertility Effects | No adverse effects on fertility reported in human studies. Anticholinergic properties do not impair reproductive function. No evidence of reduced conception rates. |
| Food/Dietary | Avoid alcohol and grapefruit juice as they may increase sedation and side effects. No significant food interactions. |
| Clinical Pearls | Doxylamine succinate is a first-generation antihistamine with strong sedative properties, commonly used as a sleep aid. Its anticholinergic effects can cause dry mouth, blurred vision, urinary retention, and constipation. Use with caution in elderly patients due to increased risk of falls, confusion, and anticholinergic toxicity. Avoid in patients with narrow-angle glaucoma, prostatic hyperplasia, or urinary retention. Onset of sedation occurs within 30 minutes; duration is 6-8 hours. Not recommended for chronic insomnia. |
| Patient Advice | Take only at bedtime due to drowsiness. · Avoid alcohol and other CNS depressants. · Do not drive or operate machinery until you know how the drug affects you. · Notify your doctor if you have glaucoma, trouble urinating, or prostate problems. · May cause dry mouth; sugarless gum or candy can help. · Do not take for more than 7-10 days without consulting a doctor. |